Archives of Pharmacy

Quantitative evaluation of dissolution profiles - from simple approaches to advanced chemometrics

Łukasz Komsta — 2024-04-28

Many forms of drugs are designed to undergo dissolution upon oral administration. The kinetics and efficiency of this process are critical parameters to be controlled. The methods of its evaluation are described in official guidelines issued by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and World Health Organization (WHO). Many approaches of comparison have been proposed, because these guidelines are not limited to a particular mathematical method. This review summarizes the current state of this topic, covering both model-dependent and model-independent methods, as well as multivariate ideas. The references have been chosen to be the most important papers in the field, so that they can be treated by the reader as the best possible recommendations for further reading.

A Comprehensive Review of the Direct Peptide Reactivity Assay in Skin Sensitization Testing: Applicability, Limitations, and Considerations

Elma Omeragić — 2024-04-28

Skin sensitization is a crucial endpoint in the safety assessment of chemicals, with the Direct Peptide Reactivity Assay (DPRA) emerging as a valuable in chemico method for evaluating a substance's sensitization potential. This review delves into the principles, applicability, and limitations of the DPRA within the context of the Adverse Outcome Pathway (AOP) framework for skin sensitization. We examine the DPRA's role in addressing the molecular initiating event of skin sensitization, its integration into Integrated Approaches to Testing and Assessment (IATA), and its performance in predicting sensitizers. The review also highlights the challenges in testing certain categories of chemicals and the importance of considering the DPRA's results alongside other complementary methods. By providing a comprehensive overview of the DPRA, this review aims to inform researchers, regulators, and clinicians about its utility and limitations in the context of skin sensitization testing.

Leveraging the Power of Supercritical Fluid Chromatography for Eco-Conscious Solutions in Pharmaceutical Analysis

Jovana Krmar — 2024-04-28

Initially employed primarily at a preparative scale for enantiomer separation of chiral drug candidates, Supercritical Fluid Chromatography (SFC) is nowadays extensively used in the analytical mode. Recent advances in SFC separation science have emphasized its potential for modern and environmentally friendly pharmaceutical analysis. The aim of this review is to provide a deeper insight into the main fundamental and practical aspects of the SFC technique in order to familiarize readers with its versatile nature and efficiency in creating sustainable chromatographic solutions. All considerations are made primarily in the context of the most widely used mode of operation - achiral SFC. In addition, recent applications of this promising technique are presented at the end of the article to further promote its use in pharmaceutical analytical practice.

Possibility of replacing conventional organic solvents with green Deep Eutectic Solvents in drug analysis

Djordje Vasilić — 2024-04-28

In recent years, Deep Eutectic Solvents (DESs) have attracted increasing attention in various scientific disciplines. Their unique properties, such as low toxicity, biodegradability, low cost and versatility, have made them an attractive alternative to conventional organic solvents. In pharmaceutical analysis, where the demand for environmentally friendly methods is growing, questions regarding whether DESs can replace organic solvents as "green solvents" have arisen. This paper explores the potential applications of DESs in drug analysis, and highlights the benefits and challenges they bring. Examples of the use of DESs in chromatographic techniques and in the extraction of drugs from various samples are presented. Additionally, research on the stability and toxicity of DESs in analytical applications is discussed. Based on the available data, it could be concluded that DESs have the potential to become an important component of analytical methods in pharmaceutical analysis and provide environmentally sustainable and efficient alternatives to conventional organic solvents. However, further research is needed to better understand their properties and optimize their application in drug analysis.

Investigation of cyclodextrin as potential carrier for lycopene

Anna Kulawik — 2024-04-28

Lycopene is a carotenoid with high antioxidant activity. Numerous studies show its positive effects in the prevention and amelioration of many diseases. However, due to its lack of water solubility, its use is very limited. Developing a formulation with lycopene with favorable therapeutic parameters will allow for a more effective use of this ingredient. The aim of this study was therefore to use supercritical phase extraction to obtain lycopene-containing preparations, and to obtain complexes of the extract with cyclodextrins to improve its solubility and increase its antioxidant potential. Lycopene-containing extracts were obtained by ultrasound-assisted acetone extraction and supercritical phase extraction. The supercritical extract was combined with γ-cyclodextrin, β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD) analyses were performed for the obtained systems and extracts. A paddle apparatus was used to evaluate the in vitro dissolution, and the samples collected were analysed by HPLC. The antioxidant activity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method. The results show that cyclodextrins increase the dissolution of lycopene into an acidic environment and enhance the antioxidant potential of the compound. We conclude that the development of a formulation containing a combination of lycopene obtained by supercritical extraction and cyclodextrin will allow for a wider and more effective use of this ingredient.

PLS based quantitative determination of insulin aspart in solution using Raman spectroscopy

Hrisanta Godzo — 2024-04-28

The complex structure of medicines containing polypeptide active substances requires the implementation of challenging analytical approaches, based on physicochemical methods, and, where necessary, biological assays for quality control, as well as for the detection of substandard and falsified products. Vibrational spectroscopic techniques, including Raman spectroscopy, are fast, powerful, and non-destructive techniques which, when combined with multivariate chemometric modelling, can provide specific identification, quantitative determination, and insight into the secondary structure of proteins and peptides. The aim of this study was to investigate the possibility of using Raman spectroscopy as a screening method for quantification of pharmaceutical products containing active substances with polypeptide structures. For that purpose, a model based on partial least square (PLS) analysis for quantitative determination of insulin aspart in solution was developed using Raman spectroscopy. The proposed model enables the establishment of a rapid approach for screening of the quality of formulations containing active substances with polypeptide structure, providing the selection of suspected samples that should be further analysed using routine techniques, which are time-consuming and costly.

Green RP-HPLC method for impurity profile of amlodipine in tablets

Olga Gigopulu — 2024-04-28

Increased awareness of nature preservation has encouraged the introduction of the green analytical chemistry (GAC) practice concepts concerning several important aspects, including sustainable development, environmental impact, and minimum waste. The aim of this research was to contribute to the implementation of this approach for the pharmaceutical industry while retaining the crucial aspects and strict requirements of quality control of medicines. Therefore, an ethanol-based, green and robust high-performance liquid chromatography (HPLC) method for the determination of related substances of amlodipine (AML) in film-coated tablets was developed and optimized using the Design of Experiments (DoE). The chromatographic separation was performed on an RP-select B column (250 x 4.0 mm, 5 μm), using a mixture of 0.04 M sodium dihydrogen phosphate monohydrate (pH 4.0) and ethanol (60:40 % v/v) as a mobile phase. The optimized conditions provided the separation of two specified impurities (impurity D and impurity F). The selectivity of the method was confirmed using forced degradation studies. The Analytical Eco-scale approach and AGREE metrics confirmed that the method conforms to the GAC principles. The validated method was successfully applied for the determination of related substances in three samples from the market, demonstrating the applicability of the method in routine analysis.

Concept of ecologically acceptable chromatographic methods: Case study on the separation of dronedarone hydrochloride and its degradation products

Nevena Djajić — 2024-04-28

Recently, concern about the environmental impact of drug analysis methods has increased significantly. Reversed-phase high-performance liquid chromatography (RP-HPLC), the predominant technique in drug analysis, relies heavily on organic solvents such as acetonitrile, which is known for its chromatographic efficiency, but also for its toxicity and flammability. To address these concerns, it is essential to minimize the use of toxic organic solvents. The aim of this study is to explore greener RP-HPLC modifications and evaluate their applicability in the pharmaceutical industry. Methods were developed for the separation of dronedarone hydrochloride and its degradation products based on experimental design, including micellar liquid chromatography (MLC), β-cyclodextrin (CD) modified RP-HPLC and ultra-high performance liquid chromatography (UHPLC). The eco-friendliness of these methods was assessed using the analytical eco-scale score, green analytical procedure index (GAPI) and analytical greenness (AGREE). AGREE appears to be the most suitable, as it revealed the greatest differences between the compared methods, as well as insights into critical aspects of the methods. UHPLC and β-CD modified RP-HPLC have been shown to be superior to MLC, and both methods can be a good choice, depending on whether the ease of implementation or energy efficiency is considered to be a more important criterion.

A novel HPLC method for the simultaneous determination of empagliflozin and dapagliflozin: Development, validation, robustness testing and greenness assessment

Eleftheria Kladi — 2024-04-28

Empagliflozin (EMPA) and Dapagliflozin (DAPA) are mainly recommended for the treatment of type 2 diabetes mellitus and heart failure. Based on the principles of green analytical chemistry, a simple, rapid and robust HPLC method was developed for the determination of both analytes in bulk. An isocratic protocol was developed using a C18 column, with a mobile phase consisting of just 30% organic modifier (ACN), while the remaining 70% was HPLC water. The run was completed within 4 min, with a flow rate of 1.20 mL/min, while UV detection took place at 230 nm. The method was then validated according to the ICH Q2 (R1) guidelines, and all the parameters examined were within the specified limits. Furthermore, the robustness of the method was evaluated by employing a factorial experimental design. Finally, the environmental friendliness of the proposed method was assessed by using the Analytical GREEness (AGREE) metric tool. The proposed method can be used for analysis of EMPA and DAPA in bulk, with potential application to the relevant pharmaceuticals.